Treatment Resistant Depression

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Table of contents

THESIS DECLARATION
ABSTRACT
ABSTRAIT
ACKNOWLEDGEMENTS
AUTHORSHIP DECLARATION: CO-AUTHORED PUBLICATIONS
LIST OF FIGURES
LIST OF TABLES
ABBREVIATIONS
CHAPTER 1: INTRODUCTION
1. NEUROMODULATION
1.1 Transcranial Magnetic Stimulation
1.2 Repetitive Transcranial Magnetic Stimulation
1.2.1 Frequency
1.2.2 Coil Shape
1.2.3 Intensity
1.3 Effects of High-Intensity rTMS
1.3.1 Synaptic Plasticity
1.3.2 Influence on Regulatory Molecules
1.3.3 Neurogenesis
1.3.4 Effects of Low Intensity rTMS
1.3.5 Summary
1.4 Therapeutic Uses of rTMS
2. DEPRESSION
2.1 Pathology
2.1.1 Monoamine Changes
2.1.2 Neuroendocrine Imbalance
2.1.3 Decreased Neurogenesis
2.1.4 Other Neurobiological Causes
2.2 Current Treatments
2.3 Treatment Resistant Depression
2.4 rTMS for the Treatment of Depression
3. ALZHEIMER’S DISEASE
3.1 Memory Decline in Alzheimer’s Disease
3.2 Pathology
3.2.1 Atrophy
3.2.2 Amyloid Plaques
3.2.3 Neurofibrillary Tangles
3.2.4 Calcium Dysregulation
3.2.6 Convergence of Theories: Synaptic Loss
3.3 Current Treatments
3.4 rTMS for the Treatment of Alzheimer’s Disease
4. ANIMAL MODELS
4.1 Animal Models of rTMS
4.1.1 Coil Size
4.1.2 Anaesthesia
4.1.3 rTMS in Animal Models of Neurological Disorder
4.2 Animal Models of Depression
4.2.1 Olfactory Bulbectomy
4.2.2 rTMS and Animal Depression Models
4.3 Animal Models of Alzheimer’s Disease
4.3.1 FAD mutations
4.3.2 PS1M146V KI mice
4.3.3 rTMS in Animal models of AD
5. THESIS SCOPE AND AIMS
CHAPTER 2: MEDIUM- AND HIGH-INTENSITY RTMS REDUCES PSYCHOMOTOR AGITATION WITH DISTINCT NEUROBIOLOGIC MECHANISMS
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
SUPPLEMENTAL METHODS AND RESULTS
CHAPTER 3: FREQUENCY DEPENDENT EFFECTS OF LOW INTENSITY RTMS IN A MURINE MODEL OF ALZHEIMER’S DISEASE
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
SUPPLEMENTARY DATA
CHAPTER 4: DISCUSSION
ALTERING THE PARAMETERS OF RTMS CAN INFLUENCE THE EFFECT IN PRECLINICAL MODELS
Intensity
Frequency
Summary – rTMS parameters
ANIMAL MODELS ARE ESSENTIAL TO ASSESS SPECIFIC ASPECTS OF NEUROLOGICAL CONDITIONS
OB model of agitated treatment resistant depression
PS1M146V model of Alzheimer’s disease
Comparison of animal models
LIMITATIONS IN ANIMAL STUDIES OF RTMS
EVIDENCE OF EFFECTIVE TAILORED TREATMENTS
Depression
Alzheimer’s Disease
CONCLUSION AND FUTURE DIRECTION
REFERENCES